Performance of comprehensive risk adjustment for the prediction of in-hospital events using administrative healthcare data: The queralt indices

Background: Accurate risk adjustment is crucial for healthcare management and benchmarking. Purpose: We aimed to compare the performance of classic comorbidity functions (Charlson's and Elixhauser's), of the All Patients Refined Diagnosis Related Groups (APR-DRG), and of the Queralt Indices, a family of novel, comprehensive comorbidity indices for the prediction of key clinical outcomes in hospitalized patients. Material and Methods: We conducted an observational, retrospective cohort study using administrative healthcare data from 156,459 hospital discharges in Catalonia (Spain) during 2018. Study outcomes were in-hospital death, long hospital stay, and intensive care unit (ICU) stay. We evaluated the performance of the following indices: Charlson's and Elixhauser's functions, Queralt's Index for secondary hospital discharge diagnoses (Queralt DxS), the overall Queralt's Index, which includes pre-existing comorbidities, in-hospital complications, and principal discharge diagnosis (Queralt Dx), and the APR-DRG. Discriminative ability was evaluated using the area under the curve (AUC), and measures of goodness of fit were also computed. Subgroup analyses were conducted by principal discharge diagnosis, by age, and type of admission. Results: Queralt DxS provided relevant risk adjustment information in a larger number of patients compared to Charlson's and Elixhauser's functions, and outperformed both for the prediction of the 3 study outcomes. Queralt Dx also outperformed Charlson's and Elixhauser's indices, and yielded superior predictive ability and goodness of fit compared to APR-DRG (AUC for in-hospital death 0.95 for Queralt Dx, 0.77- 0.93 for all other indices; for ICU stay 0.84 for Queralt Dx, 0.73- 0.83 for all other indices). The performance of Queralt DxS was at least as good as that of the APR-DRG in most principal discharge diagnosis subgroups. Conclusion: Our findings suggest that risk adjustment should go beyond pre-existing comorbidities and include principal discharge diagnoses and in-hospital complications. Validation of comprehensive risk adjustment tools such as the Queralt indices in other settings is needed

PAKistan Study of prEmature coronary atHerosclerosis in young AdulTs (PAK-SEHAT): A prospective longitudinal study protocol investigating the prevalence, severity and determinants of atherosclerotic cardiovascular disease in the young adult Pakistani population

Introduction: Atherosclerotic cardiovascular disease (ASCVD) is a major cause of morbidity, mortality and health expenditures worldwide. Despite having higher ASCVD in the Pakistani population, data on subclinical coronary atherosclerosis in young Pakistanis remain scarce. The PAKistan Study of prEmature coronary atHerosclerosis in young AdulTs (PAK-SEHAT) aims to assess the prevalence, severity and determinants of subclinical coronary atherosclerosis among Pakistani men (35-60 years) and women (35-65 years) free of clinically symptomatic ASCVD and will assess 5-year rates of ASCVD events.Methods and analysis: PAK-SEHAT is an ongoing prospective cohort study with 2000 participants from all provinces of Pakistan who will be interviewed at the baseline along with phlebotomy, measurement of carotid intima-media thickness (CIMT) and coronary CT angiography (CCTA). Phlebotomy will be repeated at 2.5 years, whereas CIMT and CCTA will be repeated at 5 years. We will report the frequency of maximal coronary stenosis ≥50% and ≥70%, number of coronary vessels with plaque and the number of coronary segments affected per participant on CCTA. We will use Cox proportional hazards regression models to evaluate the association between baseline characteristics and incident ASCVD events during follow-up. These associations will be presented as HRs with 95% CIs.Ethics and dissemination: The study protocol was approved by the Tabba Heart Institute Institutional Review Board (THI/IRB/FQ/22-09-2021/016). All study procedures are consistent with the principles of the Declaration of Helsinki. Findings of the study will be disseminated via peer-reviewed publications and conference presentations.Trial registration number: NCT05156736

Validity of ICD-9 and ICD-10 codes used to identify acute liver injury: a study in three European data sources

This is the peer reviewed version of the following article: Forns, J. [et al.]. Validity of ICD-9 and ICD-10 codes used to identify acute liver injury: a study in three European data sources. "Pharmacoepidemiology and drug safety", 6 Juny 2019, vol. 28, núm. 7, p. 965-975, which has been published in final form at 10.1002/pds.4803. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving."Purpose Validating cases of acute liver injury (ALI) in health care data sources is challenging. Previous validation studies reported low positive predictive values (PPVs). Methods Case validation was undertaken in a study conducted from 2009 to 2014 assessing the risk of ALI in antidepressants users in databases in Spain (EpiChron and SIDIAP) and the Danish National Health Registers. Three ALI definitions were evaluated: primary (specific hospital discharge codes), secondary (specific and nonspecific hospital discharge codes), and tertiary (specific and nonspecific hospital and outpatient codes). The validation included review of patient profiles (EpiChron and SIDIAP) and of clinical data from medical records (EpiChron and Denmark). ALI cases were confirmed when liver enzyme values met a definition by an international working group. Results Overall PPVs (95% CIs) for the study ALI definitions were, for the primary ALI definition, 84% (60%-97%) (EpiChron), 60% (26%-88%) (SIDIAP), and 74% (60%-85%) (Denmark); for the secondary ALI definition, 65% (45%-81%) (EpiChron), 40% (19%-64%) (SIDIAP), and 70% (64%-77%) (Denmark); and for the tertiary ALI definition, 25% (18%-34%) (EpiChron), 8% (7%-9%) (SIDIAP), and 47% (42%-52%) (Denmark). The overall PPVs were higher for specific than for nonspecific codes and for hospital discharge than for outpatient codes. The nonspecific code “unspecified jaundice” had high PPVs in Denmark. Conclusions PPVs obtained apply to patients using antidepressants without preexisting liver disease or ALI risk factors. To maximize validity, studies on ALI should prioritize hospital specific discharge codes and should include hospital codes for unspecified jaundice. Case validation is required when ALI outpatient cases are considered.Peer ReviewedPostprint (author's final draft

Real-World Epidemiology of Potassium Derangements Among Chronic Cardiovascular, Metabolic and Renal Conditions: A Population-Based Analysis

Background: The aims of the present analysis are to estimate the prevalence of five key chronic cardiovascular, metabolic and renal conditions at the population level, the prevalence of renin-angiotensin-aldosterone system inhibitor (RAASI) medication use and the magnitude of potassium (K+) derangements among RAASI users. Methods and Results: We used data from more than 375,000 individuals, 55 years of age or older, included in the population-based healthcare database of the Catalan Institute of Health between 2015 and 2017. The conditions of interest were chronic heart failure (CHF), chronic kidney disease (CKD), diabetes mellitus, ischemic heart disease and hypertension. RAASI medications included angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, mineralocorticoid receptor antagonists (MRAs) and renin inhibitors. Hyperkalemia was defined as K+ levels >5.0 mEq/L and hypokalemia as K+ <3.5 mEq/L. The prevalence of chronic cardiovascular, metabolic and renal conditions was high, and particularly that of hypertension (prevalence ranging from 48.2% to 48.9%). The use of at least one RAASI medication was almost ubiquitous in these patients (75.2-77.3%). Among RAASI users, the frequency of K+ derangements, mainly of hyperkalemia, was very noticeable (12% overall), particularly in patients with CKD or CHF, elderly individuals and users of MRAs. Hypokalemia was less frequent (1%). Conclusion: The high prevalence of K+ derangements, and particularly hyperkalemia, among RAASI users highlights the real-world relevance of K+ derangements, and the importance of close monitoring and management of K+ levels in routine clinical practice. This is likely to benefit a large number of patients, particularly those at higher risk

Discordance between 10-year cardiovascular risk estimates using the ACC/AHA 2013 estimator and coronary artery calcium in individuals from 5 racial/ethnic groups: Comparing MASALA and MESA

Background and aims: South Asian (SA) individuals are thought to represent a group that is at high-risk for atherosclerotic cardiovascular disease (ASCVD). However, the performance of the Pooled Cohort Equations (PCE) remains uncertain in SAs living in the US. We aimed to study the interplay between predicted 10-year ASCVD risk and coronary artery calcium (CAC) in SAs compared to other racial/ethnic groups. Methods: We studied 536 SAs from the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study, and 2073 Non-Hispanic Whites (NHWs), 1514 African Americans (AAs), 1254 Hispanics, and 671 Chinese Americans (CAs) from the Multi-Ethnic Study of Atherosclerosis (MESA) who were not currently on statins. We used logistic regression models to assess the association between race/ethnicity and CAC within each ASCVD risk stratum. Results: SAs at low and at intermediate estimated ASCVD risk were more likely to have CAC = 0 compared to NHWs, while SAs at high risk had a similar CAC burden to NHWs. For example, intermediate-risk SAs had a 73% higher odds of CAC = 0 compared to NHWs (95% 1.00-2.99), while high-risk SAs were equally likely to have CAC = 0 (OR 0.95, 95% CI 0.65-1.38) and CAC > 100 (OR 0.86, 95% CI 0.61-1.22). Conclusions: Our results suggest that the extent of ASCVD risk overestimation using the PCEs may be even greater among SAs considered at low and intermediate risk than among NHWs. Studies with incident ASCVD events are required to validate and/or recalibrate current ASCVD risk prediction tools in this group

Study Design and Cohort Comparability in a Study of Major Cardiovascular Events in New Users of Prucalopride Versus Polyethylene Glycol 3350

INTRODUCTION: Given prior safety experience with other 5-HT4 agonists for chronic constipation, an observational, population-based cohort study in five data sources from Germany, Sweden, and the UK was conducted to evaluate the cardiovascular safety of prucalopride. OBJECTIVES: Our objective is to describe the methods and resulting comparability of cohorts in a multi-database, multinational study of prucalopride initiators and polyethylene glycol 3350 (PEG) initiators following a harmonized protocol. METHODS: Prucalopride initiators were matched on age, sex, and index date to PEG initiators (1:5 ratio). Study exposures, cardiovascular risk factors, and other covariates were identified from healthcare utilization codes harmonized across databases. Cardiovascular outcomes were identified using database-specific algorithms based on diagnosis codes. The propensity score (PS) in each database was estimated using logistic regression, with prucalopride versus PEG as the outcome and including clinically relevant variables associated with major adverse cardiovascular events. RESULTS: In total, 12,030 prucalopride initiators and 59,985 PEG initiators were identified. After matching and trimming, cohorts from the UK and Sweden were well-balanced for cardiovascular risk factors and cancer. However, in Germany, PEG initiators remained older and sicker than prucalopride initiators. The prevalence of these characteristics also differed from those in the UK and Sweden. The pooled analyses included only data from the UK and Sweden. CONCLUSIONS: Matching, trimming, and PS stratification yielded comparable cohorts in four of five data sources. Use of these methods could not achieve balance for key covariates within the German cohort, likely due to reimbursement differences in Germany

Cardiovascular Safety of Prucalopride in Patients with Chronic Constipation:A Multinational Population-Based Cohort Study

INTRODUCTION: The serotonin 5-HT4 receptor agonist prucalopride is approved in the European Union for the treatment of chronic constipation. This offered the unique opportunity to include real-world observational data on cardiovascular safety in the new drug application for approval of prucalopride in the USA. METHODS: This observational population-based cohort study (EUPAS9200) conducted in five data sources (three in the UK, one in Sweden, and one in Germany [which was subsequently excluded from the pooled analyses]) aimed to estimate the pooled adjusted incidence rate ratio for major adverse cardiovascular events (defined as hospitalization for non-fatal acute myocardial infarction or stroke, and in-hospital cardiovascular death) in adult initiators of prucalopride compared with initiators of polyethylene glycol 3350 (PEG) following a common protocol. Standardized incidence rates and incidence rate ratios of major adverse cardiovascular events were derived using propensity score stratification. Sensitivity analyses explored the impact of exposure definition, outcome categories, interim cancer, and unmeasured confounding. RESULTS: The pooled analyses included 5715 initiators of prucalopride and 29,372 initiators of PEG. Average duration of use was 175 days for prucalopride and 82 days for PEG. The pooled standardized incidence rate per 1000 person-years (95% confidence interval) of major adverse cardiovascular events was 6.57 (3.90–10.39) for patients initiating prucalopride and 10.24 (6.97–14.13) for PEG. The pooled adjusted incidence rate ratio for major adverse cardiovascular events was 0.64 (95% confidence interval 0.36–1.14). Results remained consistent in various sensitivity analyses. CONCLUSIONS: The pooled incidence rate ratio estimate was consistent with no indication of an increased risk above the pre-specified safety threshold of 3.00 for major adverse cardiovascular events in patients with chronic constipation using prucalopride as compared with PEG